Program Three: "Dangerous Friends and Friendly Enemies"

A Friendly Enemy (Part 7 of 10)

A look at the common food pathogen called Salmonella and how it spreads. And the hunt for the cause of English Sweating Sickness that once ravaged the English countryside in the 15th and 16th centuries.




{Title: A "Friendly" Enemy}

Narrator, Lillian Lehman: At Stanford University, Stanley Falkow and his student are learning how some microbes have evolved the capability to outwit the human immune system. The focus of their research is Salmonella. A group of bacteria which cause typhoid fever, and diarrhea. Salmonella are different from the deadly enemy Hantavirus. Seen here, reproducing at three hundred and sixty times normal speed. Salmonella has learned to be a friendly enemy. Unlike the Hantavirus, Salmonella kills some human cells, when it invades them to get food, but usually the human host survives.

Scientist, Stanley Falkow: While Salmonella food poisoning is common, the number of people who actually get infected by Salmonella, from food every year, that don't show disease, is much, much greater then the people who show disease.

Narrator, Lillian Lehman: Salmonella bacteria have learn to defeat the bodies defensive mechanisms. They enter with contaminated food, or water. In the mouth, salmonella survive competing organisms, sticky saliva, and bacteria killing chemicals. In the stomach, they withstand churning in an acid bath. In the small intestine, they survive bile salts designed to rip microbes apart. They aim towards specialized cells that line the walls of the intestine, as part of the immune system's defenses. Salmonella has leaned through evolution, how to defeat this protective cell, and pass right through. Across roams the Macrophage, a type of white blood cell, designed to destroy invaders like viruses, or Salmonella. Salmonella not only survive inside the Macrophage, and reproduce, they kill it, and burst out to infect more cells.

Scientist, Stanley Falkow: This interaction, usually its a draw, the organism got food, it made more of itself, and passed on to a new person to make more of itself. And we're happy because we can now recognize this organism and will be immune to it. Now occasionally it doesn't turn out so well for us, and the organism gets the upper hand. It's then that we see, what we call, infectious disease.

Narrator, Lillian Lehman: One of Stan Falkow's students, Denise Monack, used a microscope to video tape the interaction of Salmonella with a Macrophage, the killer cell.

Student, Denise Monack: I couldn't remember if this is the one that goes into a tubular.

Scientist, Stanley Falkow: That's right, this is one of the, yeah, this is the mystery, now.

Student, Denise Monack: Right.

Scientist, Stanley Falkow: And when you watch this interaction, you see the bacteria coming into contact. And quickly the cell gobbles them up. It's almost like it's eating peanuts. I mean, it's taking them in as quickly as it can. And most bacteria that fall into the clutches of a macrophage die a horrible death. Salmonella responds by turning on new sets of genes, that change the macrophage. And the end result really is, the organism grows in the macrophage, and eventually kills the macrophage.

Narrator, Lillian Lehman: Although the macrophage may die, we normally don't. Salmonella has successfully evolved to infect us without killing us, ensuring its survival. Other microbes peacefully living inside our bodies, can suddenly become enemies, if we take an antibiotic to fight against that Salmonella attack, our internal microbial balance can be disrupted. And some of our microbial friends die as a side effect of the antibiotic. Then a small population of one kind of bacteria, resistant to the antibiotic can begin to take over.

Scientist, Stanley Falkow: It's really um, found something that must be like Nirvana to a microbe, and it begins to grow. And as it begins to grow, one of its by products is really toxic to human cells.

Narrator, Lillian Lehman: The side effect of that antibiotic, can be diarrhea, caused by internal microbes, that are usually benign. Our dance with microbes, ranges from the cooperative, to the hostile. The threat from Hantavirus, and some other microbes, is like a conflict frozen in time. It seems to appear, and reappear. Lying dormant in between. Sometimes for centuries.

{Title: "Well in the morning, Dead by Supper"}.

Narrator, Lillian Lehman: Four hundred years ago in the English country side, a mysterious resperatory disease terrorized Tudor England. It was called the English Sweating Sickness, for the high fevers it induced.
There were five outbreaks of this dreaded killer, between fourteen eighty five, and fifteen fifty one. The disease even changed the course of history by taking the life of young prince Arthur Tudor. His younger brother, Henry the VIII, became king, paving the way for the English reformation. Then the sweat disappeared entirely. For over four hundred years in metropolitan London, there has not been a single documented case of the sweating sickness. It was almost forgotten. That is, until three medical detectives suspected a connection between the sweating sickness and Hantavirus.

Doctor, Vanya Gant: Richard.

Doctor, Richard: Morning.

Doctor, Vanya Gant: Good moring.

Narrator, Lillian Lehman: Dr. Vanya Gant is a physician at Saint Frances Hospital in London, which specializes in infectious disease.

Doctor, Vanya Gant: Are these, they?

Doctor, Richard: Uh, these are them.

Narrator, Lillian Lehman: In the fall of nineteen ninety seven he was approached by a medial student named Guy Thwaites, who when researching for his graduation project, had stumbled across a historical record to 'the sweat'.

Doctor, Vanya Gant: Which was now in his tracheal side. And he said in the sixteenth, the late fifteenth, and the sixteenth century in England, there seemed to be a disease that was characterized by fever, and rapid death. I said go and find out about it, and we'll talk. Let's see if we can build this up.

Narrator, Lillian Lehman: They teamed up with Mark Taviner, a sixteenth century historian who could translate the old English, and Latin of ancient records. The three of them set out to solve one of England's oldest medical mysteries. The sweating sickness so affected Tudor England that it was the subject of one of the first books printed about disease. It described all the symptoms, besides high fever, and sweating.

Student, Guy Thwaites: The clinical descriptions, as best described, were of a very rapid onset. One would feel flu like. You'd have joint pains, headache, feel a little bit under the weather, and then a gathering shortness of breath to the point where some twenty four to forty eight hours later, you were dead.

Doctor, Vanya Gant: I said, this sounds exactly like the four corners disease, the Hantavirus pulmonary syndrome that had been described maybe two, three years beforehand in the south western corner of the United States. I mean we knew that Hantaviruses, probably had been around in ancient times. Way before christ from Chinese texts.

Narrator, Lillian Lehman: Guy Thwaites, and Mark Taviner set out to find a broader source of information. Their richest came from gravediggers' records and old parish registers.

Student, Guy Thwaites: Parish records are important because they are some of the only surviving documents, and often include the cause of death. Many of the descriptions would describe someone as being Well at, well in the morning, and dead by supper.

Historian, Mark Taviner: This must be it.

Student, Guy Thwaites: There it is. Here it is.

Historian, Mark Taviner: Yeah, this is it.

Narrator, Lillian Lehman: Then they found a description by an architectural historian, of a unusually large and artful tomb stone. The stone marked the grave of the Duke of Suffolk, and his younger brother, who both died in fifteen fifty one. The year of the last recorded outbreak of the Sweating Sickness.

Historian, Mark Taviner: You can see that the area is depressed.

Narrator, Lillian Lehman: Historian, Mark Taviner.

Historian, Mark Taviner: The Dukes are of particular interest. Because they were important enough for this to have been written about. They were studying with their tutor at Cambridge University, which is about fifteen miles away, as the crow flies. And, as the sweat spread through the country it stuck Cambridge. And the boys fearing for their lives, fled, and when they got here they fell sick.

Narrator, Lillian Lehman: The accumulating evidence, lead Guy Thwaites to be more and more convinced that the sweating sickness was caused by some kind of Hantavirus.

Student, Guy Thwaites: It was certainly a summer disease. It was not a disease that was associated with poor conditions of sanitation. It was scattered. It was rural. It didn't conform to any patterns of people to people transmission. It conformed more to, some other factor involved in its transmission. We believe that this is where the rodent theory comes in.

Narrator, Lillian Lehman: The identity of the microbe which caused the English Sweating Sickness may never definitely established. However, this research adds a intriguing chapter, to one of Europe's longest running medical mysteries.

Student, Guy Thwaites: What we see in modern medicine is just a snapshot. We don't see anything other than that. We don't look at history in modern medicine. We don't get taught it in our medical schools. Perhaps we should be. Perhaps we ought to get more perspective on the evolution of infectious diseases. We think that we are seeing them for the first time, but we're, we're not seeing them for the first time. This is a cyclical thing. They reappear and appear, and have done so throughout the whole of history.

Narrator, Lillian Lehman: For most of human history, our lack of knowledge about the microbial world, left us at the mercy of infectious diseases. Microbes take advantage of any opportunity, poverty, and lack of sanitation, give them those opportunities. There's no need to travel back in time, to find an example.

(Transcript provided by Tyler Anderson)



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